1. Field
Provided is a three-helix bundle protein, a polynucleotide encoding the three-helix bundle protein, a method of preparing the three-helix bundle protein, an agent for inhibiting HDM2 and/or HDMX including the three-helix bundle protein as an active ingredient, and a pharmaceutical composition for preventing and/or treating a cancer including the three-helix bundle protein as an active ingredient.
2. Description of the Related Art
HDM2 and/or HDMX (or HDM4), are negative regulators of the tumor suppressor p53, and act by stimulating p53 ubiquitination, thereby leading to the degradation of p53 by the proteosome in a cell. HDM2 and/or HDMX are reported to be over-expressed in various kinds of cancers and interact with p53 by recognizing and binding to the transcription activation domain (TAD) positioned at the N-terminus of p53 through direct protein-protein interaction (PPI). Therefore, the development of antagonists capable of inhibiting the PPI in order to prevent intracellular p53 degradation may provide new cancer therapeutics. One such PPI antagonist, Nutlin-3, has been shown to inhibit only the binding of HDM2 and p53, and has a high level of cytotoxicity.
Therefore, there is a need to develop new compounds capable of effectively inhibiting degradation of p53 by HDM2 and/or HDMX that have low cytotoxicity. This invention provides such compounds.